In many cases, an electrochemical glucose measuring system may have an elevated oxidation current due to the oxidation of interfering compounds commonly found in physiological fluids such as, for example, acetaminophen, ascorbic acid, bilirubin, dopamine, gentisic acid, glutathione, levodopa, methyldopa, tolazimide, tolbutamide, and uric acid. The accuracy of glucose meters may, therefore, be improved by reducing or eliminating the portion of the oxidation current generated by interfering compounds. Ideally, there should be no oxidation current generated from any of the interfering compounds so that the entire oxidation current would depend only on the glucose concentration.
It is, therefore, desirable to improve the accuracy of electrochemical sensors in the presence of potentially interfering compounds such as, for example, ascorbate, urate, and, acetaminophen, commonly found in physiological fluids. Examples of analytes for such electrochemical sensors may include glucose, lactate, and fructosamine. Although glucose will be the main analyte discussed, it will be obvious to one skilled in the art that the invention set forth herein may also be used with other analytes.
Oxidation current may be generated in several ways. In particular, desirable oxidation current results from the interaction of the redox mediator with the analyte of interest (e.g., glucose) while undesirable oxidation current is generally comprised of interfering compounds being oxidized at the electrode surface and by interaction with the redox mediator. For example, some interfering compounds (e.g., acetominophen) are oxidized at the electrode surface. Other interfering compounds (e.g., ascorbic acid), are oxidized by chemical reaction with the redox mediator. This oxidation of the interfering compound in a glucose measuring system causes the measured oxidation current to be dependent on the concentration of both the glucose and any interfering compound. Therefore, in the situation where the concentration of interfering compound oxidizes as efficiently as glucose and the interferent concentration is high relative to the glucose concentration, the measurement of the glucose concentration would be improved by reducing or eliminating the contribution of the interfering compounds to the total oxidation current.
One known strategy that can be used to decrease the effects of interfering compounds is to use a negatively charged membrane to cover the working electrode. As an example, a sulfonated fluoropolymer such as NAFION™ may be used to repel all negatively charged chemicals. In general, most interfering compounds such as ascorbate and urate have a negative charge, thus, the negatively charged membrane prevents the negatively charged interfering compounds from reaching the electrode surface and being oxidized at the surface. However, this technique is not always successful since some interfering compounds such as acetaminophen do not have a net negative charge, and thus, can pass through a negatively charged membrane. Nor would this technique reduce the oxidation current resulting from the interaction of interfering compounds with some redox mediators. The use of a negatively charged membrane on the working electrode could also prevent some commonly used redox mediators, such as ferricyanide, from passing through the negatively charged membrane to exchange electrons with the electrode.
Another known strategy that can be used to decrease the effects of interfering compounds is to use a size selective membrane on top of the working electrode. As an example, a 100 Dalton exclusion membrane such as cellulose acetate may be used to cover the working electrode to exclude all chemicals with a molecular weight greater than 100 Daltons. In general, most interfering compounds have a molecular weight greater than 100 Daltons, and thus, are excluded from being oxidized at the electrode surface. However, such selective membranes typically make the test strip more complicated to manufacture and increase the test time because the oxidized glucose must diffuse through the selective membrane to get to the electrode.
Another strategy that can be used to decrease the effects of interfering compounds is to use a redox mediator with a low redox potential, for example, between about −300 mV and +100 mV (when measured with respect to a saturated calomel electrode). Because the redox mediator has a low redox potential, the voltage applied to the working electrode may also be relatively low which, in turn, decreases the rate at which interfering compounds are oxidized by the working electrode. Examples of redox mediators having a relatively low redox potential include osmium bipyridyl complexes, ferrocene derivatives, and quinone derivatives. A disadvantage of this strategy is that redox mediators having a relatively low potential are often difficult to synthesize, unstable and have a low water solubility.
Another known strategy that can be used to decrease the effects of interfering compounds is to use a dummy electrode which is coated with a redox mediator. In some instances the dummy electrode may also be coated with an inert protein or deactivated redox enzyme. The purpose of the dummy electrode is to oxidize the interfering compound at the electrode surface and/or to oxidize the redox mediator reduced by the interfering compound. In this strategy, the current measured at the dummy electrode is subtracted from the total oxidizing current measured at the working electrode to remove the interference effect. A disadvantage of this strategy is that it requires that the test strip include an additional electrode and electrical connection (i.e., the dummy electrode) which cannot be used to measure glucose. The inclusion of dummy electrode is an inefficient use of an electrode in a glucose measuring system.